PGfAR and Diabetes UK - Joint funding call on remission of Type 2 diabetes
Programme Grants for Applied Research (PGfAR) is partnering with Diabetes UK. In Competition 34, which launched in October 2020, co-funding was available for programmes of applied research that investigate the implementation, in primary care, of approaches to help people recently diagnosed with Type 2 diabetes put the condition into remission. These may be new interventions, or other approaches that complement existing programmes in order to optimise engagement or effectiveness. Competition 34 closed in November 2020.
Type 2 diabetes currently accounts for 10% of total healthcare expenditure in the UK  and can severely impact on the quality of life of those living with the condition . Remission from Type 2 diabetes is defined by having two measurements of an HbA1c below 48mmol/mol at least six months apart having stopped all glucose-lowering therapies . Putting diabetes into remission has been shown to have the potential to deliver significant benefits in both quality of life and health economic terms . Achieving remission decreases ten year cardiovascular risk scores from 23% to 7% : these data lay the basis for future research on how remission can decrease complications and comorbidities.
Remission was first shown to be possible following substantial weight loss achieved through bariatric surgery . Recent research has shown that total diet replacement programmes providing around 810 kcal/day can also result in remission [7,8], and that this can be sustained for at least 2 years in a proportion of people who take part . In 2018, the NHS commissioned a pilot based on a total dietary replacement approach as part of the new NHS long term plan , which started in September 2020. However, there are many questions remaining relating to remission and a need for further research.
The Diabetes Research Steering Groups identified remission as a key priority in the diabetes research landscape. Research recommendations to address some of these questions were published following a workshop on remission hosted by Diabetes UK in July 2019 . Among the areas identified were a number of key questions relating to the implementation of remission programmes, highlighting in particular the need for additional evidence-based approaches to induce and maintain weight loss and a need for further understanding of the psychological impact of remission, and the effects of these programmes in terms of physical and psychosocial wellbeing for people who do not go into remission.
Whilst advances in supporting people to put their Type 2 diabetes into remission have been significant, there are still many for whom existing programmes do not work. Even with the ‘best in class interventions’, as many as 54% allocated to total dietary replacement and 42% to gastric bypass bariatric surgery do not reach remission . While these rates are affected by the amount of weight lost and duration of diabetes, there are significant barriers and challenges to these interventions, and different approaches may be more effective for different people. There is evidence that implementing programmes offering alternative or complementary approaches, including food-based methodologies [13 14, 15], or additional psychological support [16, 17], could increase the number of people who reach remission.
The importance of this issue to people with the condition and healthcare professionals was highlighted by its identification as the number one priority raised by the type 2 diabetes James Lind Alliance Priority Setting Partnership: “Can type 2 diabetes be cured or reversed, what is the best way to achieve this and is there a point beyond which the condition can't be reversed?”.
NIHR Programme Grants for Applied Research (PGfAR) and Diabetes UK are inviting applications for collaborative, multidisciplinary programmes of applied research which aim to investigate the implementation, in primary care or the community, of new approaches with clear potential for putting Type 2 diabetes into remission within 12 months of diagnosis. These can include programmes to enhance the effectiveness, engagement or longevity of the remission effect.
Applications should fall within the remit of the PGfAR programme. Applications should also contain a comprehensive updated summary of previous high quality research on this topic, and should ensure that there is no significant overlap with the ongoing pilot of total dietary replacement low calorie diets within the NHS nor be dependent on data from this pilot.
Applications are expected to provide evidence supporting their rationale and likely effectiveness (plausibility for generating remission of type 2 diabetes), sustainability and potential cost effectiveness. Applications should be co-designed with people with Type 2 diabetes or those who have gone through remission, and the outcomes studied should also focus on the impact the intervention has on people living with Type 2 diabetes and take into account both quality of life /psychosocial impacts and the real world implementation of such interventions.
Such approaches may, for example, include one or more of:
- different nutrition-based programmes for achieving remission.
- novel approaches to supporting weight loss maintenance, such as third wave cognitive behavioural therapies, either as part of a new intervention or alongside existing approaches.
- combining pharmacotherapy with nutrition-based programmes
- strategies for improving psychosocial support for people attempting to achieve remission or those who have completed a remission intervention, regardless of their outcome.
- ways to identify those who respond well or poorly to existing interventions, or to triage people to the most effective treatments to maximise their reach and benefit
The programme of research and any interventions should focus on recruiting people with Type 2 diabetes who are within 12 months of diagnosis, but should exclude people diagnosed with Type 2 diabetes under 30 years of age or those who have also been diagnosed with an eating disorder, prolonged depression, diabetes distress or severe mental illness. Applications with a focus on equality diversity and inclusion would also be particularly welcomed.
- Hex N, Bartlett C, Wright D, Taylor M, Varley D. Estimating the current and future costs of Type 1 and Type 2 diabetes in the UK, including direct health costs and indirect societal and productivity costs. Diabet Med. 2012;29(7):855-862. doi:10.1111/j.1464-5491.2012.03698.x
- Rubin, R.R. and Peyrot, M. (1999) Quality of life and diabetes. Diabetes Metab. Res. Rev., 15: 205-218.
- Nagi, Dinesh, et al. “Remission of Type 2 Diabetes: a Position Statement from the Association of British Clinical Diabetologists (ABCD) and the Primary Care Diabetes Society (PCDS).” British Journal of Diabetes, vol. 19, no. 1, 2019, pp. 73–76.
- Xin et al, Diabetologia 2020 and Rehovacka L et al. Acceptability of a very-low-energy diet in Type 2 diabetes: patient experiences and behaviour regulation Diabetic Med 2017; 34: 1554–1567
- Taylor & Barnes, Diabetic Medicine 2019; 36, 308–315
- Herbst CA, Hughes TA, Gwynne JT, Buckwalter JA. Gastric bariatric operation in insulin-treated adults. Surgery 1984;95:209–214.
- Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia. 2011;54(10):2506-2514. doi:10.1007/s00125-011-2204-7
- Steven S, Hollingsworth KG, Al-Mrabeh A, et al. Very Low-Calorie Diet and 6 Months of Weight Stability in Type 2 Diabetes: Pathophysiological Changes in Responders and Nonresponders [published correction appears in Diabetes Care. 2018 Apr 24;:]. Diabetes Care. 2016;39(5):808-815. doi:10.2337/dc15-1942
- Xin Y, Davies A, McCombie L, et al. Within-trial cost and 1-year cost-effectiveness of the DiRECT/Counterweight-Plus weight-management programme to achieve remission of type 2 diabetes. Lancet Diabetes Endocrinol. 2019;7(3):169-172. doi:10.1016/S2213-8587(18)30346-2
- Very Low Calorie Diets Part of NHS Action to Tackle Growing Obesity and Type 2 Diabetes Epidemic. NHS Choices, NHS. Accessed 10/09/2019
- Hopkins, M., Andrews, R., Salem, V., Taylor, R., le Roux, C., Robertson, E. and Burns, E. (2020) Improving understanding of type 2 diabetes remission: research recommendations from Diabetes UK’s 2019 remission workshop. Diabet. Med. Accepted Author Manuscript.
- Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric surgery versus intensive medical therapy for diabetes--3-year outcomes. N Engl J Med. 2014;370(21):2002-2013. doi:10.1056/NEJMoa1401329
- Unwin, DJ, et al. Substantial and Sustained Improvements in Blood Pressure, Weight and Lipid Profiles from a Carbohydrate Restricted Diet: An Observational Study of Insulin Resistant Patients in Primary Care. Int J Environ Res Public Health 2019; 16:15
- Remission of pre-diabetes to normal glucose tolerance in obese adults with high protein versus high carbohydrate diet: randomized control trial. Stentz FB, Brewer A, Wan J, Garber C, Daniels B, Sands C, Kitabchi AE. BMJ Open Diabetes Res Care. 2016 Oct 26;4(1):e000258.
- Control of blood glucose in type 2 diabetes without weight loss by modification of diet composition. Gannon MC, Nuttall FQ. Nutr Metab (Lond). 2006 Mar 23;3:16
- Lawlor ER, Islam N, Bates S, Griffin SJ, Hill AJ, Hughes CA, et al. Third-wave cognitive behaviour therapies for weight management: A systematic review and network meta-analysis. Obesity Reviews. 2020;21(7):e13013.
- Lillis J, Thomas JG, Niemeier HM, Wing RR. Exploring process variables through which acceptance-based behavioral interventions may improve weight loss maintenance. Journal of Contextual Behavioral Science. 2017;6(4):398-403
- Finer S, Robb P, Cowan K, Daly A, Robertson E, Farmer A, Top ten research priorities for type 2 diabetes: results from the Diabetes UK–James Lind Alliance Priority Setting Partnership. The Lancet Diabetes & Endocrinology, 29 October 2017. d
In Competition 32, launched in February 2020, co-funding was available for proposals which aimed to prevent or slow the progression of diabetes complications in people with Type 1 or Type 2 diabetes who are at extremely high risk. The brief for this call is available here.
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